The priority review may have a lot to do with lung cancer rates in China, which continue to rise (unlike the trend in Western nations), with NSCLC the most common form of the disease—not to mention that fact that supporting data showed that Alecensa significantly reduced the risk of disease progression or death by more than half compared to crizotinib. ALK-positive NSCLC is a distinct form of NSCLC, commonly affecting younger people (median age 52) and those with a light or non-smoking history. Approximately 5 percent of NSCLC cancer cases are ALK-positive.

“[This] approval marks a new era for ALK-positive lung cancer patients in China, who now have a treatment option that offers a meaningful, sustained benefit compared with the previous standard of care,” said Dr. Sandra Horning, Roche’s chief medical officer and head of global product development. “It also represents a significant regulatory shift, with the approval received under unprecedented timelines. We are proud to be at the forefront of healthcare innovation in China by helping to bring Alecensa to patients as quickly as possible.”

The China approval was based on primary analyses from the global Phase 3 ALEX study, assessing Alecensa versus crizotinib in the first-line treatment of people with ALK-positive metastatic NSCLC; the pharmacokinetics results in Asian patients from the Phase 3 ALESIA study, also investigating Alecensa compared to crizotinib in the first-line setting; and two Phase 2 studies assessing Alecensa in patients who have progressed on or are intolerant to crizotinib.

In updated analyses of the ALEX study that were presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, the primary endpoint of investigator-assessed progression-free survival (PFS) was more than tripled in people who received Alecensa compared to those who received crizotinib (34.8 months vs. 10.9 months)

Further supporting the use of Alecensa in this setting, the ALESIA study—which met its primary endpoint and showed that Alecensa as a first-line treatment significantly reduced the risk of PFS compared to crizotinib in Asian patients with ALK-positive NSCLC—will be submitted to the CNDA to complete a post-approval agreement. This is the third Phase 3 study to show that Alecensa was superior as an initial treatment compared to crizotinib in this type of lung cancer, according to Roche. Full results from the ALESIA study will be presented at an upcoming medical meeting.

Key data from the ALEX study presented at the ASCO meeting included:

Alecensa reduced the risk of disease worsening or death (also referred to as PFS) by 53 percent compared to crizotinib

Alecensa reduced the risk of progression in the central nervous system (CNS) by 84 percent

The 12-month cumulative rate of CNS progression for people with or without existing CNS metastases at baseline was 9.4 percent for people treated with Alecensa and 41.4 percent for people treated with crizotinib

Grade 3 to 5 adverse events (AEs) were less frequent in the Alecensa arm (41 percent) compared to the crizotinib arm (50 percent). In the Alecensa arm, the most common Grade 3 to 5 AEs were increased liver enzymes and decreased red blood cells. AEs leading to discontinuation were all lower in the Alecensa arm compared to the crizotinib arm.

Follow-up results from the ALEX study analysis were also presented at the ASCO meeting and included:

After a further 10 months of follow-up, Alecensa reduced the risk of disease progression or death by 57 percent compared to crizotinib. Median follow-up was 27.8 months vs. 22.8 months for Alecensa-treated patients and crizotinib-treated patients, respectively

Investigator-reported median PFS (the primary endpoint) was 34.8 months in the Alecensa arm vs. 10.9 months in the crizotinib arm

Overall response rate for people treated with Alecensa was 82.9 percent compared to 75.5 percent for people treated with crizotinib, as assessed by the investigator

Alecensa demonstrated superior efficacy compared to crizotinib regardless of the presence or absence of CNS metastases at baseline.

Grade 3 to 5 AEs were less frequent in the Alecensa arm (44.7 percent) compared to the crizotinib arm (51.0 percent). The most common Grade 3 to 4 AEs were increased liver enzymes and increased muscle enzymes. AEs leading to dose reduction and dose interruption were both lower in the Alecensa arm compared with the crizotinib arm. AEs leading to discontinuation were equal in both arms.

“Follow-up results from the ALEX study demonstrate the significant sustained benefit of Alecensa, showing that people with metastatic ALK-positive non-small cell lung cancer lived for almost three years without their disease progressing,” Horning remarked in a May news release. “These results further support the use of Alecensa as a standard of care for people who are newly diagnosed with this form of lung cancer.”

Alecensa is a highly selective, CNS active, oral medicine created at Chugai Kamakura Research Laboratories and is being developed for people with NSCLC whose tumors are identified as ALK-positive. It is now approved in over 57 countries as an initial treatment for ALK-positive, metastatic NSCLC.